Evidence map›Paper›PMID 39543689›Full record

ArticleStem cell research & therapy2024

Endothelial progenitor cell-derived conditioned medium mitigates chronic cerebral ischemic injury through macrophage migration inhibitory factor-activated AKT pathway.

Ya-Wen Cheng, Ling-Yu Yang, Yi-Tzu Chen, Sheng-Che Chou, Kuo-Wei Chen, Yi-Hsing Chen, Chuan-Rou Deng, I-Chin Chen, Wan-Ju Chou, Chen-Chih Chang and 4 more

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Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Ya-Wen ChengDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Ling-Yu YangDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Yi-Tzu ChenDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Sheng-Che ChouDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Kuo-Wei ChenDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Yi-Hsing ChenDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Chuan-Rou DengDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
I-Chin ChenDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Wan-Ju ChouDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan.
Chen-Chih ChangDepartment of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Yong-Ren ChenNon-Invasive Cancer Therapy Research Institute, Taipei, Taiwan.
Hsiao-Lin HwaDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
Kuo-Chuan WangDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan. wang081466@yahoo.com.tw.
Meng-Fai KuoDivision of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, 100, Taiwan. mfkenator@gmail.com.ORCID 0000-0002-1803-2719

Funding

Ministry of Science and Technology, Taiwan 108-2314-B-002-085-MY2Ministry of Science and Technology, Taiwan 108-2314-B-002-086Ministry of Science and Technology, Taiwan 109-2314-B-002-124Ministry of Science and Technology, Taiwan 110-2314-B-002-159Ministry of Science and Technology, Taiwan 110-2314-B-002-160-MY2Ministry of Science and Technology, Taiwan 111-2314-B-002-254-MY2Ministry of Science and Technology, Taiwan 112-2314-B-002-240National Taiwan University NTU-NFG-113L7469
6 · The paper itself

Abstract

backgroundChronic cerebral ischemia (CCI) is a significant health issue characterized by hypoperfusion due to damage or occlusion of the cerebral or carotid arteries. CCI may lead to progressive cognitive impairment that is considered as a prelude to neurodegenerative diseases, including dementia and Alzheimer's disease (AD). Endothelial progenitor cells (EPCs) have been implicated in vascular repair in ischemic cerebrovascular diseases, primarily by differentiating into endothelial cells (ECs) or through paracrine effects. However, the clinical transplantation of stem cell therapies remains limited. In this study, we investigated the effects of EPC-derived conditioned medium (EPC-CM) on the impaired vasculature and neurological function in a rodent model of CCI and the mechanism involved.

methodsEPC-CM was analyzed by cytokine array to identify key factors involved in angiogenesis and cellular senescence. The effects and mechanism of the candidate factors in the EPC-CM were validated in vitro using oxygen-glucose deprivation (OGD)-injured ECs and EPCs. The therapeutic effects of EPC-CM and the identified key factor were further examined in a rat model of CCI, which was induced by bilateral internal carotid artery ligation (BICAL). EPC-CM was administered via intracisternal injection one week post BICAL. The cerebral microvasculature and neurobehavior of the rats were examined three weeks after BICAL.

resultsMacrophage migration inhibitory factor (MIF) was identified as a key factor in the EPC-CM. Recombinant MIF protein promoted angiogenesis and prevented senescence in the injured EPCs and ECs. The effect was similar to that of the EPC-CM. These therapeutic effects were diminished when the EPC-CM was co-treated with MIF-specific antibody (Ab). Additionally, the vascular, motor, and cognitive improvements observed in the BICAL rats treated with EPC-CM were abolished by co-treated with MIF Ab. Furthermore, we found MIF promoted angiogenesis and anti-senescence via activating the AKT pathway. Inhibition of the AKT pathway diminished the protective effects of MIF in the in vitro study.

conclusionsWe demonstrated that EPC-CM protected the brain from chronic ischemic injury and promoted functional recovery through MIF-mediated AKT pathway. These findings suggest EPC-CM holds potential as a novel cell-free therapeutic approach for treating CCI through the actions of MIF.

Indexed as

Brain IschemiaEndothelial Progenitor CellsMacrophage Migration-Inhibitory FactorsProto-Oncogene Proteins c-aktRats, Sprague-DawleyAnimalsCulture Media, ConditionedDisease Models, AnimalHumansIntramolecular OxidoreductasesMaleRatsSignal TransductionCulture Media, ConditionedIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMif protein, ratProto-Oncogene Proteins c-aktAKT pathwayCerebral ischemiaEndothelial progenitor cell-derived conditioned mediumMacrophage migration inhibitory factor

Identifiers

PMID39543689
PMCPMC11566597

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.